Sodium Carbonate → HCID 67045153, compound

HRID 2203934Notes

Reaction equation

HRID 2203934 reaction equation
[CH3:1][C:2]1(C)[C:6](C)(C)OB(C(C)=C)O1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:20]1[C:21]([N:42]2[CH2:47][CH2:46][CH2:45][C@@H:44]([NH:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:43]2)=[C:22]2[C:28]([NH:29][C:30](=[O:34])[CH:31]([CH3:33])[CH3:32])=[CH:27][N:26]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:23]2=[N:24][CH:25]=1.CC#N.O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:52]([O:51][C:49]([NH:48][C@@H:44]1[CH2:45][CH2:46][CH2:47][N:42]([C:21]2[C:20]([C:2]([CH3:6])=[CH2:1])=[CH:25][N:24]=[C:23]3[N:26]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH:27]=[C:28]([NH:29][C:30](=[O:34])[CH:31]([CH3:33])[CH3:32])[C:22]=23)[CH2:43]1)=[O:50])([CH3:54])([CH3:53])[CH3:55]

Participants

7

Reactant 4

HCID 10340Sodium Carbonate2×HCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane2×HCID 18373917Acetonitrile--water (1/1)HCID 67045601HCID 67045601, compound

Product 1

HCID 67045153HCID 67045153, compoundYield 50.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

4,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (174 mg, 1.03 mmol), PS-palladium tetrakis (470 mg, 0.0517 mmol, 0.10 mmol/1 g) and 2N sodium carbonate (775 μL, 1.55 mmol) were added to (R)-tert-butyl 5-bromo-4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-3-isobutyramido-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (300 mg, 0.517 mmol; Example 81, Step A) in degassed dioxane (1 mL). The reaction was heated to 120° C. for 1 hour under microwave irradiation. 4,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (174 mg, 1.03 mmol) and 2N sodium carbonate (775 μL, 1.55 mmol) were added, and the reaction was heated to 120° C. for an additional 2 hours. The reaction mixture was then cooled down and filtered. The filtrate was diluted with DCM washed with water. The layers were separated. The organic phase was dried (MgSO4) and concentrated, and the resulting residue was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 15-100% CH3CN/water) to yield (R)-tert-butyl 4-(3-(tert-butoxycarbonylamino)piperidin-1-yl)-3-isobutyramido-5-(prop-1-en-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (141 mg, 50% yield) as a solid.

Workup

  1. temperaturethe reaction was heated to 120° C. for an additional 2 hours
  2. temperatureThe reaction mixture was then cooled down
  3. filtrationfiltered
  4. additionThe filtrate was diluted with DCM
  5. washwashed with water
  6. customThe layers were separated
  7. dry with materialThe organic phase was dried (MgSO4)
  8. concentrationconcentrated
  9. customthe resulting residue was purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record
ord-771aa090fd694f489982d55d81daab35
Source dataset
uspto-grants-2016_06
Patent number
US09365568B2

Reaction notes

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